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Clinical Trial
. 2024 Aug 16;230(2):e486-e495.
doi: 10.1093/infdis/jiae075.

Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine

Nelli Westercamp  1 , Lawrence Osei-Tutu  2 , Lode Schuerman  3 , Simon K Kariuki  4 , Anne Bollaerts  3 , Cynthia K Lee  5 , Aaron M Samuels  1   6 , Christian Ockenhouse  5 , Dennis K Bii  4 , Samuel Adjei  2 , Martina Oneko  4 , Marc Lievens  3 , Maame Anima Attobrah Sarfo  2 , Cecilia Atieno  4 , Ashura Bakari  2 , Tony Sang  4 , Maame Fremah Kotoh-Mortty  2 , Kephas Otieno  4 , François Roman  3 , Patrick Boakye Yiadom Buabeng  2 , Yaw Ntiamoah  2 , Daniel Ansong  2 , Tsiri Agbenyega  2 , Opokua Ofori-Anyinam  3
Affiliations
Clinical Trial

Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine

Nelli Westercamp et al. J Infect Dis. .

Abstract

Background: The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.

Methods: In total, 1500 children aged 5-17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).

Results: At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%-49%) to 53% (R012-14-26; 95% CI: 42%-62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).

Conclusions: Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.

Clinical trials registration: NCT03276962 (ClinicalTrials.gov).

Keywords: RTS, S/AS01E; fractional-dose regimen; malaria vaccine; vaccine efficacy; vaccine impact.

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Conflict of interest statement

Potential conflicts of interest. L. S., A. Bo., M. L., F. R., and O. O.-A. are GSK employees. L. S., F. R., and O. O.-A. have restricted shares in GSK. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Vaccine efficacy against all episodes of clinical malaria meeting the secondary (A, C) and primary (B, D) case definitions up to study months 26 (A, B) and 32 (C, D), overall and by country (exposed set). Error bars represent 95% CIs. The trial was not powered to assess vaccine efficacy by country. M, month; N, number of children; PY, person-years; VE, vaccine efficacy; CI, confidence interval.
Figure 2.
Figure 2.
Vaccine impact expressed as cumulative number of clinical malaria cases averted (all episodes, secondary case definition) per 1000 children vaccinated or per 1000 RTS,S/AS01E (RTS,S) full-dose equivalents administered, overall (exposed set). The estimated number of malaria cases averted was calculated as the area under the incidence curve of clinical malaria meeting the secondary case definitions captured in 3-month increments for each group (sum of the differences in incidence between the RTS,S and control groups summed over all the 3-month periods included in the period considered). Panels on the left represent the point estimates for all RTS,S groups at the 3-month interval, with the colored areas representing the 95% CIs with the highest upper limit and lowest lower limit, respectively, among the 4 estimates. For clarity, panels on the right represent values for each RTS,S group separately; areas represent 95% CIs. CI, confidence interval.
Figure 3.
Figure 3.
Vaccine impact expressed as cumulative number of clinical malaria cases averted (all episodes, secondary case definition) per 1000 children vaccinated or per 1000 RTS,S/AS01E (RTS,S) full-dose equivalents administered in Ghana (A) and Kenya (B) (exposed set). The estimated number of malaria cases averted was calculated as the area under the incidence curve of clinical malaria meeting the secondary case definitions captured in 3-month increments for each group (sum of the differences in incidence between the RTS,S and control groups summed over all the 3-month periods included in the period considered). Panels on the left represent the point estimates for all RTS,S groups at the 3-month interval, with the colored areas representing the 95% CIs with the highest upper limit and lowest lower limit, respectively, among the 4 estimates. For clarity, panels on the right represent values for each RTS,S group separately; areas represent 95% CIs. CI, confidence interval.
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References

    1. World Health Organization . World malaria report 2022. Available at: https://www.who.int/teams/global-malaria-programme/reports/world-malaria.... Accessed 8 August 2023.
    1. World Health Organization . Malaria vaccine: WHO position paper—March 2022. Wkly Epidemiol Rec 2022; 97:61–80.
    1. World Health Organization . WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization. Available at: http://www.who.int/news/item/02-10-2023-who-recommends-r21-matrix-m-vacc.... Accessed 8 January 2024.
    1. Chandramohan D, Zongo I, Sagara I, et al. . Seasonal malaria vaccination with or without seasonal malaria chemoprevention. N Engl J Med 2021; 385:1005–17. - PubMed
    1. World Health Organization . WHO position on the use of fractional doses—June 2017, addendum to vaccines and vaccination against yellow fever WHO: position paper—June 2013. Vaccine 2017; 35:5751–2. - PubMed

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